CD8+ T cell-mediated inflammation in the CNS CD8+ T cells, among the first mononuclear cells responding to an infection, are important participants in the steps initiating brain inflammation which can be salutary or harmful. Recently, a study from this laboratory showed protective CD8+ T cell activity against murine brain infection with Cryptococcus neoformans, the facultative intracellular fungus that causes cryptococcal meningoencephalitis. Murine cryptococcosis is an easily manipulated model system with which this laboratory has had significant success in understanding resistance to an important CMS pathogen. Since viral pathogens often deploy products that subvert and inhibit normal host cell transcription and/or translation, selected non-viral intracellular CMS pathogens may be better choices for model systems in which to dissect differential gene expression in the infected brain cell, or antigen presenting cell, likely the brain-resident macrophage, or microglial cell. We plan to examine the cytokine/chemokine elements of cross-talk between microglia and CD8+ cells and to investigate whether CD8+ CTL is a significant immune mechanism deployed against these non-viral brain infections, thus advancing our understanding of an important but poorly-understood aspect of brain immune function.